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Challenges in Diagnosis and Management of
Dengue in Adults:
Interesting Dengue Cases
ศ.นพ. ธีระพงษ์ ตัณฑวิเชียร MD., FRCP(Edin)
อาจารย์หน่วยโรคติดเชื้อ ภาควิชาอายุรศาสตร ์
คณะแพทยศาสตร ์ จุฬาลงกรณ์มหาวิทยาลัย
หัวหน้า Tropical Medicine Cluster, Health Supercluster,
จุฬาลงกรณ์มหาวิทยาลัย
ผู้ช่วยผู้อานวยการและรักษาการหัวหน้าฝ่ายวิจัยและบริการคลินิค
สถานเสาวภา สภากาชาดไทย
VV-MEDMAT-69501: Jun 2022
2
Disclosure ( 2016-2022)
Prof. Terapong Tantawichien: has received support for
Travel for International Conference (Bionet, Siam Pharm)
Lectureships (GlaxoSmithKline, Pfizer, MSD, Roche
Thai Meiji, Siam Pharm, Sanofi , Biovalys, Biogenetec……).
Advisory board for zoster vaccine/pneumococcal vaccine (MSD),
rabies vaccine (GSK), dengue vaccines (Sanofi, MSD, Takeda),
influenza vaccine(Sanofi)
Prof. Terapong Tantawichien: has received research funds from
Sanofi (C. difficile vaccine) 2016-17
Medico (Plant-derived influenza vaccine) 2017-18
MPH, Thailand (shorten rabies PET) 2019-20
NSTDA/Bionet (Asia)-Spearhead project
(Tdap: recombinant pertussis toxin)-2019-2023)
Sanofi (Rabies vaccine:VRV-12) 2020-2021
Sanofi (Rabies vaccine: VRV-14) 2020-2021
Baiya ( Covid-19 vaccine) 2021-2023
Sanofi ( Yellow fever vaccine) 2021-2025
Jansen ( RSV vaccine) 2022-2024
Overview
• Dengue in Adults: Shifting of age groups in Thailand
• Burden of Dengue in Adults: Focus on elderly and
patients with co-morbidities
• Diagnosis and Clinical Management in Adult Dengue:
How to get better care
• Significant co-circulation of the dengue viruses and
• COVID-19 could have on health system in dengue endemic area
• COVID-19 or dengue infection:
Increase risk of infection and morbidity
Differential diagnosis of dengue and COVID-19
False positive serological tests for dengue /COVID-19 infections
Coinfections by COVID-19 and dengue virus: Increased severity
• Impact of lockdown and social distancing on dengue epidemics
Decreased/increased incidence of dengue
Wartel TA; Asia Pacific Journal of Public Health 2017, Vol. 29(1) 7–16
Period(1980-2010)
Incidence increased in all countries:
Annual average % change (AAPC) 1980-2010:
6.7% in Thailand
10.4% in Vietnam
12.0% in Indonesia
18.1% in Malaysia
24.4% in Philippines
Mortality: Increased in Indonesia (6.8%), Malaysia(7%),
Philippines(29.2%)
Decreased in Thailand(-1.3%), Vietnam (−2.5%)
Indonesia Malaysia
Philippines Thailand
Vietnam
0.0
10.0
20.0
30.0
40.0
50.0
60.0
70.0
80.0
90.0
Age <15
Age >15
Proportion of Dengue Cases in Children and Adults, Thailand, 2000 - 2019
National Notifiable Disease Information System, Brazil MoH, prepared by João Bosco Siqueira Jr.
| 6
SPGLB.DENG.14.12.0103
ALL AGE GROUPS ARE AT RISK OF DENGUE DISEASE
Thailand
Dengue in Bangkok 2015
0
20
40
60
80
100
< 15 years
%
Mortality rate < 0.1%
> 15 yrs
Age-specific dengue seroprevalence in Mueang Rayong district, Thailand, according to the
A) 1980, and B) 2010 serosurveys. Rodríguez-Barraquer I; Am J Epidemiol 2014
1980 - 96% exposed by age 11 years,
2010 -only 82% exposed by age 18 years.
MAT-GLB-2102556 v1.0 Jun 2021
| 10
Dengue seroprevalence in HCW in Thailand
(PRNT50 )
Seropositive : PRNT50 ≥ 10, Seronegative : PRNT50 < 10
• 400 HCW age 21-60 years old, (13% men, 87% women)
• High dengue seroprevalence in study population,
• 95% (379/400) have PRNT50 ≥10 for at least one serotypes
• 11% (45/400) has PRNT50 < 10 for all serotypes
WP. Vandepitte, Southeast Asian J Trop Med Public Health, Vol 50 No. 5 September 2019
Serotype 1
Serotype 2
Serotype 3
Serotype 4
By Serotype and Age Group
1
1
Angkana T. Huanga; PNAS 2022 Vol. 119 No. 20 e2115790119 https://doi,
The mean age of dengue
hemorrhagic fever (DHF) cases
increased considerably in
Thailand from 8.1 to 24.3 y
between 1981 and 2017 (mean
annual increase of 0.45 y).
Alternative proposed explanations for
this trend, such as
- changes in surveillance practices,
- reduced mosquito–human contact,
- shifts in population demographics,
have different implications for global
dengue epidemiology
Source: BOE, MoPH, Annual Epidemiology Surveillance Report (2010 to 2014), Report 506(2015)
0-4 17 12% 8 13% 14 16% 11 8% 6 12% 13 9%
5-9 41 29% 17 27% 19 22% 27 20% 8 16% 17 11%
10-14 29 21% 12 19% 20 23% 29 21% 8 16% 20 14%
15-24 29 21% 7 11% 19 22% 36 26% 12 24% 37 25%
25-34 8 6% 8 13% 11 13% 23 17% 5 10% 25 17%
35-44 7 5% 4 6% - 0% 4 3% 6 12% 20 14%
45-54 5 4% 6 10% 3 3% 3 2% 2 4% 13 9%
55-64 1 1% - 0% 1 1% 3 2% 2 4% 2 1%
65+ 2 1% 1 2% - 0% - 0% - 0% 1 1%
Total 139 63 87 136 49 148
Number and percentage of reported Deaths from dengue per age group
2010 2011 2012 2013 2014 2015
ALL ALL
11% 17% 5% 7% 20% 24%
Age
group
ALL ALL ALL ALL
Deaths from Dengue in Thailand
Deaths from Dengue in Thailand 2018 ( 6 months)
Age Symptom Dengue Per 100,000 Dengue Death %
0 – 4 1,481 42.3 2 0.14
5 – 14 8,146 101.4 8 0.1
15 - 34 8,994 48.3 13 0.14
35 - 59 3,208 12.3 10 0.31
> 60 710 6.5 5 0.70
Overview
• Dengue in Adults: Shifting of age groups in Thailand
• Burden of Dengue in Adults: Focus on elderly and
patients with co-morbidities
• Diagnosis and Clinical Management in Adult Dengue:
How to get better care
28 adult dengue deaths, median age was 59 yrs and co-morbidities 75%.
Probable dengue was diagnosed in 32.1% by WHO 1997 criteria
and 78.6% by WHO 2009.
The earliest warning sign was persistent vomiting at a median of 1.5 days. Hematocrit change
>20% concurrent with platelet count <20 × 10^9/L was associated with the shortest interval to
death at a median of 3 days.
Only 35.7% of death cases fulfilled DHF criteria by WHO 1997 versus severe dengue in
100.0% by WHO 2009 criteria.
Deaths were due to shock and organ failure. Acute renal impairment occurred in 71.4%,
impaired consciousness 57.1% and severe hepatitis 53.6%.
Confirmed adult dengue deaths in Singapore: 5-year multi-center
retrospective study. Leo et al. BMC Infectious Diseases 2011, 11:123
Dengue cases hospitalized;58.1% (2007 epidemic) 28.9% (2013–2014 epidemic)
Less than 2% of hospitalized patients were admitted to the ICU.
The proportions of dengue cases hospitalized and patients admitted to the ICU were highest in elderly aged > 65 y
Risk predictors of progression to severe disease during the febrile phase of dengue: a
systematic review and meta-analysis Sorawat Sangkaew; Lancet Infect Dis 2021;21: 1014–26
Findings Of 122 articles comprising 25 potential predictors were included in the meta-analyses.
Female patients had a higher risk of severe dengue than male patients in the main analysis (16·2% VS
10·5%[OR=1·13] but not in the subgroup analysis of studies with children.
Pre-existing comorbidities associated with severe disease were
DM 31·3% VS 16·0%; crude OR 4·38
Hypertension 35·0% VS 20·6% OR 2·19
Renal disease 45·8% VS 16·0 OR 4·67
Cardiovascular disease 23·1% VS 8·6% OR 2·79
References:
1. Toh ML, et al. Comorbidities increase In-Hospital Mortality in Dengue Patients in Brazil. Poster presented at API congress , 17 May 2017
The average age of dengue patients admitted to ICU was around 42 years old, and 58% the male sex.
50% of these patients had medical comorbidities like DM, HT, cardiac disorders, chronic kidney,liver disease.
30% of patients had hypotension needing vasopressor therapy, 26%with RF needing ventilation,
and 17% with renal failure needing renal replacement therapy.
The ICU mortality was 20%. (? Medical comorbidity, pre-treatment , bacterial infection….)
Overview
• Dengue in Adults: Shifting of age groups in Thailand
• Burden of Dengue in Adults: Focus on elderly and
patients with co-morbidities
• Diagnosis and Clinical Management in Adult Dengue:
How to get better care
Dengue infection
(DEN-1,Den-2,DEN-3, DEN-4)
Symptomatic(25%) Asymptomatic(75%)
J Clin Virol 2007
Southeast Asian J Trop Med Public Health 2013
WHO Guideline 2009
During the COVID-19 pandemic, distinguishing dengue from cases of COVID-19 in endemic areas can be difficult.
Tertiary hospital: Strategy of routine COVID-19 testing for febrile patients with viral prodromes was used.
(designated ward-PPE) , 11,086 admissions were screened for COVID-19;
868 cases of COVID-19/ 380 cases of dengue.
8.5% of suspected COVID-19 cases were tested for dengue serology due to a compatible overlapping syndrome, and
dengue was established as an alternative diagnosis in 2% (207/10,218) of suspected COVID-19 cases that tested
negative. 8 COVID-19 cases with likely false-positive dengue serology and one probable coinfection.
From April to May 2020, 251 admissions presenting as viral prodromes with no RTI
15 cases had COVID-19, and 2/15 had false-positive dengue IgM.
Potential antigenic cross-reactivity between SARS-CoV-2and Dengue viruses
Yaniv Lustig; Clin Infect Dis 2020
Serology characteristics of 14 patients with covid-19 (n 55) and false positive dengue serology
SD Bioline PanBio
Tun-Linn Thein; Am. J. Trop. Med. Hyg., 90(6), 2014, pp. 984–987
1,921 confirmed adult dengue patients between 2005 and 2008.
We found that severe neutropenia, defined as ANC < 0.5 + 109/L, was found in
11.8% with a median duration of 1 day. ANC nadir occurred on illness day 5.
Severe neutropenia was not predictive of more severe disease and not
associated with secondary bacterial infections, prolonged hospital stay,
prolonged fever, or fatal outcome.
Anon Srikiatkhachorn ; Thromb Haemost 2009
Warning signs
Dengue/severe dengue
Warning signs
Dengue/severe dengue
Dengue fever Dengue hemorrhage fever
Who Guideline 2009
DHF
14- yr boy
DF
16- yr boy
DHF
14- yr boy
DF
16- yr boy
“Dengue is one disease
entity with different clinical
presentations and often with
unpredictable clinical
evolution and outcome”
Who Guideline 2009
Who Guideline 2009
RCPT guideline- Thailand
Indications for hospitalization ( one of the followings ):
• - Signs/symptoms that physicians considers make the admission of
the patient necessary (eg. intractable nausea/vomiting,
serious illness etc.)
- Significant bleeding eg. gastrointestinal bleeding etc.
- Dengue shock syndrome (DSS)
- Hematocrit > 50 %
- Platelet < 20,000/ mm3 ( < 20x109/L)
- AST or ALT > 500 IU/mL
- Acute renal failure, hepatic failure, heart failure,
alteration of consciousness, severe hypoxemia
- Pregnant woman
- Morbid obesity
- Patients could not follow up as out-patient setting
Management of Adult Dengue
Bleeding in adult dengue:
Severe Gastrointestinal bleeding
Anticoagulant
Prophylaxis platelet transfusion
Leakage syndrome (DHF) and DSS in adults
Fluid overload/myocardial injury
Liver injury and GI manifestations
Hepatitis / Acetaminophen usage
Acute hepatic failure
Others:
Renal failure- metabolic acidosis
Co-infection-bacteremia
If major bleeding occurs it is usually from GI tract, and/or vagina in adult females.
Internal bleeding may not become apparent for many hours until the first black stool is passed.
Patients at risk of major bleeding are those who had:
– Prolonged/refractory shock;
– Hypotensive shock and renal or liver failure and/or severe and
persistent metabolic acidosis;
– Received non-steroidal anti-inflammatory agents
– Pre-existing peptic ulcer disease
– Received anticoagulant therapy
– Trauma, including intramuscular injection.
Day of fever 4 5 6 7 8 9
39
BT 38
37
21 year-old patient (male)
DEN - IgM positive
stable
N/V cough hematemesis/melena hematochexia
diarrhea Rx PRC endoscope (DU active bleeding)
myalgia platelet conc. vagotomy/pyloroplasty
Hct
WBC/mm3
N / L (%)
Platelet/mm3
CXR
40
5500
74/15
150,000
40
4700
65 / 28
42,000
26
59,000
normal
21 19 25 30 32
12500
61 / 38
72,000(PT/PTT-N) 69,000 97,000
normal
BP
Characteristics and predictors for gastrointestinal hemorrhage among adult patients
with dengue virus infection: Emphasizing the impact of existing comorbid disease(s)
Wen-Chi Huang: PLOS ONE 2018; https://doi.org/10.1371/journal.pone.0192919
Retrospective study : 1300 adults dengue
175 (mean age, 56.5±13.7 yrs) patients with GI bleeding
1,125 (mean age, 49.2±15.6 yrs) without GI bleeding (controls)
Results
175 patients with GI bleeding, DHF was found in 119 pts (68%).
Endoscopic exam: Gastric ulcer 52%, erythematous gastritis 33%,
duodenal ulcer 29%, erosive gastritis 29%, hemorrhagic gastritis 14.3%
Overall, GI bleeding died, giving an in-hospital mortality rate of 5.1%.
Multivariate analysis: Risk of GI bleeding:
Age> 60 years (OR 1.663)
End stage renal disease with comorbidities (OR: 9.405)
Previous stroke with comorbidities (OR: 9.772)
Gum bleeding (OR: 1.732), petechiae (OR: 2.109)
Platelet count <50×109 cells/L (OR: 3.419)
Chiu YC, Am J Trop Med 2005
Patients having PU with recent
hemorrhage require more
transfusions with PRBCs and FFP
for management of UGI bleeding
than do those without recent
hemorrhage.
PU with recent hemorrhage is
encountered during an endoscopic
procedure, endoscopic injection
therapy is not an effective adjuvant
treatment of hemostasis in dengue
patients with UGI bleeding.
A FATAL CASE OF SPONTANEOUS RUPTURE OF THE
SPLEEN DUE TO DENGUE VIRUS INFECTION: CASE
REPORT AND REVIEW. Southeast Asian J Trop Med Hyg 2008
Apatcha Pungjitprapai, Terapong Tantawichien.
Severe bleeding can be recognized by:
– Severe overt bleeding, regardless of Hct level
– Decrease in Hct after fluid resuscitation
together with unstable hemodynamic status;
– Refractory shock that fails to respond to
consecutive fluid resuscitation of 40-60 ml/kg
– Hypotensive shock with low/normal Hct before
fluid resuscitation
– Persistent or worsening metabolic acidosis
+ a well-maintained systolic blood pressure,
especially in those with severe abdominal
tenderness and distension. Jacqueline Deen, Lucy Lum, Eric Martinez, Lian Huat Tan.
Dengue: guidelines for diagnosis, treatment, prevention and control -- New edition. WHO 2009
Risks of bleeding:
INR > 3
Age > 65 years,
uncontrolled hypertension
bleeding tendencies,
Abnormal renal or liver function,
Previous stroke,
Labile INR while onwarfarin,
Concomitant use of NSAIDs
Risks of valvular thrombosis:
(ex. thromboembolism)
INR < 2
Prosthetic mitral valve
replacement,
Use of mechanical valves,
thrombophilia,
atrial fibrillation,
low left ventricular ejection fraction,
Prior thromboembolism,
Early post-operative period after
valvular replacement
Lionel Hon Wai Lum; International Journal of Cardiology 199 (2015) 432–434
Lack of efficacy of prophylactic platelet transfusion for severe
thrombocytopenia in adults with acute uncomplicated dengue infection.
Lyn DC; Clin Infect Dis 2009
Thrombocytopenia in dengue infection raises concerns about bleeding
risk. Of 256 patients with dengue infection who developed
thrombocytopenia (platelet count, < 20 x 103 platelets/microL) without
prior bleeding, 188 were given platelet transfusion.
Subsequent bleeding, platelet increment, and platelet recovery were
similar between patients given transfusion and patients not given
transfusion. Prophylactic platelet transfusion was ineffective in
preventing bleeding in adult patients with dengue infection.
Open-label, randomized, superiority trial:
We recruited patients aged > 21 years who had laboratory-confirmed or probable dengue and
thrombocytopenia (≤20 000 platelets per μL), without persistent bleeding.
Results:
Clinical bleeding by day 7/ hospital
discharge
21% in transfusion group VS
26% in control group
(risk difference –4・98% ;
RR 0.8 [95% CI 0.56-1.17]; p=0.16).
13 adverse events in transfusion
group VS 2 in the control group
(5.81% ; RR 6.26; p=0・0064).
Cardiovascular manifestations
- Plasma leakage in DHF/DSS-Hypotension
Volume overload/ pulmonary edema
Co-morbidity- CHF, coronary heart disease
- Cardiac complications-
are not uncommon but it was self-limiting,
acute myocarditis may be clinically severe.
- Myocardial dysfunction/myocarditis
Decreased EF, diastolic volume, ST-T change,
increased cardiac enzyme
-Cardiac arrhythmia-Tachy/Bradyarrhythmia
Sinus bradycardia, SVT, atrial fibrillation
APC, PVC, 1st degree AV block, 2nd degree AV block Mobitz type 1
Apichai K; Intensive Care Med 2003
V. LA-ORKHUN; Annals of Tropical Paediatrics (2011) 31, 123–128
Cardiovascular sequelae of dengue
fever: a systematic review
Abdur Rahim; Expert Rev Cardiovasc Ther . 2022
Jun 2;1-15.
ECG abnormalities (30.6%):
Sinus bradycardia (8.8%),
Nonspecific ST-T changes (8.6%),
ST depression (7.9%),
T-wave inversion (2.3%).
Mechanical sequelae were present in
10.4%, including left ventricular (LV)
systolic dysfunction (5.7%), and
myocarditis (2.9%).
Management of adult Dengue : Royal Colladge Physician of Thailand Guideline 2013
Plasma leakage( any one of this )
1.Hct≥50 %
2.Evidence of plasma leakage
➢hemoconcentration ( Hct ≥20% compare to previous Hct)
➢Pleural effusion
➢Hypotension
➢Serum albumin
Plasma leakage+
Dengue : clinical stage 2
➢Fluid: crytaloid: NSS, RLS etc
➢Close monitoring
➢Look for : hypotension, pulse pressure ≤20
mmHg, poor tissue perfusion
BP normal + pulse
pressure > 20 mmHg
Rx Oral/IV fluid :adjust
rate by
➢Clinical observation
➢Follow the Hct
➢ Urine volume and urine
specific gravity
Causes of fluid overload
– Excessive and/or too rapid IV fluids;
– Incorrect use of hypotonic
– Inappropriate use of large volumes of IV
fluids in patients without
leakage/ severe bleeding
– Continuation of IV fluids after plasma
leakage has resolved (24–48 hours
from defervescence)
– co-morbid conditions such as congenital
or ischaemic heart disease, chronic
lung and renal diseases.
WHO Guideline 2009
Mirinda CH; Clin Infect Dis 2013
81 dengue pts (mean age 32yr) –12 patients (15%): elevated biomarker levels.
Compared to controls, Higher leukocyte (P < .001) and platelet counts (P = .005);
higher CRP(P = .02), and a lower VL (P = .03).
There was no difference according to clinical dengue classification; DF/DHF/DSS ; duration of
symptoms; or prevalence of secondary infection between the 2 groups.
2 patients died secondary to cardiogenic shock before imaging studies. Necroscopic findings
were compatible to myocarditis in both , 10 patients who underwent echocardiography:
Depressed left ventricular ejection fraction (LVEF) was identified in 1,
left ventricular segmental abnormalities with preserved LVEF in 2,
and an important pericardial effusion with tamponade in another.
56
Major acute cardiovascular events after dengue infection–A population-based
observational study Kai-Che Wei; PLOS Neglected Tropical Diseases | https://doi.org/10.1371/journal.pntd.0010134 February 7, 2022
The Incident rate ratio (IRR) of MACEs
was 17.9 (95% CI 15.80–20.37) during the
first week after the onset of DENV infection
observed from 1,244 eligible patients.
IRR were significantly higher for hemorrhagic
stroke (10.9, 95% CI 6.80–17.49),
ischemic stroke (15.56, 95% CI 12.44–19.47),
AMI (13.53, 95%CI 10.13–18.06), and
heart failure (27.24, 95% CI 22.67–32.73).
No increased IRR was observed after day 14.
| 57
Footer goes here
A 24-year-old male presented fever and N/V for 4 days.
PH : Healthy, no alcohol drinking
PE : Conscious, not pale , no jaundice
VT BT 38.9°c PR 80/min BP –stable RR 24/min
Others – WNL
Lab : Hct 42 % WBC 4200/cumm N 65% L 30%M 5 %
Platelet 80,000 / cumm
BUN/Cr 10/0.8 SGOT / SGPT 5650/2690
Electrolyte -WNL
- Nausea/ vomiting
- Diarrhea
- GI bleeding
- Liver complication:
Abnormal transaminase ( increased AST and ALT)
Viral factor (DEN3,DEN4)
Prolonged shock , ischemic hepatitis
Reye’s syndrome
Drug-induced liver injury
Co-infection: Viral hepatitis A, B,C,E
Pre-existing liver diseases
- Ascites, acute appendicitis
GI Manifestations in dengue
Liver function test in DF/DHF patients
Kuo CH* Kalaganaroaj S** Tantawichien T.
DF DF DHF DF DHF
n=230 n=20 n=21 n=38 n=30
Age:Mean+SD
AST : Mean+SD
Range
ALT : Mean+SD
Range
Bilirubin :
Abnormal/range
Akaline phasphatase
Abnormal/range
41+12
220+341
17-3210
146+178
8-1177
7.2%0.2-35
16%320-536
3.7+1
64+46
35+18
4.3+1.2
124+166
51+59
28.6+13.2
258+436
17-2128
184+255
19-1171
0%
all<1.5
23.4+7.6
399+554
15-2580
261+321
3-1382
1 case (5)
all<1.5
*Kuo CH; Am J Trop Med Hyg 1992
**Kalayanarooj S; JID 1997
Patterns and causes of liver involvement in acute dengue infection
Fernando et al. BMC Infectious Diseases (2016) 16:319
AST
ALT
AST/ALT ratio
Effect of Standard Dosage of Paracetamol versus Placebo as
An Antipyretic Therapy on Transaminitis in Adult Dengue
Infection: A Randomized Controlled Trial Vasikasin V: Presented in RCPT 2018
Multicenter randomized ,double trial, placebo control:
125 hospitalized adult patient (mean age 27 + 10 yrs) with laboratory-confirmed dengue
If body temp. > 38 °c – received paracetamol 500 mg or placebo 500 mg every 4 hrs
Primary outcome- AST and ALT more than 3 times
Results
Median daily dosage of paracetamol 1.5g ( IQR= 0.8-2g)
- Significant higher rate of transiminitis (increased AST,ALT) in
paracetamol group compared with placebo
(22% vs 10%; incidence rate ratio 3·77,p= 0·011).
- The change of AST/ALT in the paracetamol group > placebo group
(mean difference AST= 12·43 U/L per day, p<0·0001
ALT=; 7·40 U/L per day, p=0·0001
No significant change of body temp. and pain score
Day of fever 4 5 6 7 8 9 10 11
39
BT 38
37
BP stable Bradycardia
Fever no diarrhea Anti HAVIg M
N/V N/V N/V Anti HB c IgM
AntiHCV
Anti HIV
Others
Hct 42 44
WBC/mm 4200 2,200
N/L (%) 65 /25 100 / 70
Platelet/mm3 80.000 47,000
SGOT/SGPT 5650/2690 849/862(TB/DB 4.5/3.5) 324/287( TB 2)
AP 152 Albumin 3.5
Hemoculture neg
no pleural effusion
24 year - old patient (male)
80/
Acute hepatic failure
in Hemoglobin H dis and DHF
Recent suggestions for the treatment of dengue patients with
acute liver failure
N-acetylcysteine (NAC)
Providing temporary liver support – Artificial liver support
Treeprasertsuk S; Southeast Asian J Trop Med Public Health 2015
World J Hepatol 2021 December 27; 13(12): 1968-1976
A Thai male 34-year-old patient underlying Ch Hepatitis B
And alcoholic drinking – no treatment
Ultrasound- mild splenomegaly, SGOT/SGPT-WNL
CC: Fever 4 days PTA
PI: 4 days PTA high fever, diarrhea, N/V and myalgia
2 days PTA fever, jaundice, yellow stool
( he ate paracetamol 20 tab and cpm+pseudoephrindine 8 tab )
PE: Good consciousness, not pale, mark jaundice
VT- PR 98/min, RR 24/min, BP 150/80mmHg, BT 38 °c
Chest/heart- WNL
Abdomen- soft, not tender, liver 2 FB below RCM(span 15 cm)
no ascites, BS normal
LAB: Hct 44.4 % WBC 9,000/mm3 N 59,L23 , Atypical L 6
Platelet 90,000 /mm3
Hct 43 % WBC 13,000/mm3 N 59, L30 ,Platelet 49,000 /mm3
Na 131, K4.3, Cl 92, HCO3 27
LFT- TB 8.2mg%, DB 6.7mg%,SGOT/SGPT 2333 / 1404 ,
Alb 3.7 mg% ,BUN/Cr 24/1 mg%, PT 17.3/11.2 CPK 118
Dengue IgM/IgG- rapid test Positive
Dengue NS1 –positive
Dengue IgM-positive
Dengue IgG-positive
HbsAg -positive
AntiHBc-positive
AntiHCV-negative
US- Cirrhosis, no ascites
Treatment
Supportive treatment, hydration
Drugs : Acetaminophen,Anti-gastritis ; H2 blocker,NSAIDs
Unnecessary drugs; muscle relaxant……
Antibiotic treatment ( 20-30 % case )
Transfusion : Platelet transfusion, PRC, FFP
Procedure : catheter, NG tube, endoscopy, operation
Adjunctive therapy : Steroid, IVIG
Carbazochrom sodium sulfonate (AC-17),
Recombinant activated factor VII,
Desmopressin
6
8 Population-based assessment of factors influencing antibiotic prescribing for
adults with dengue infection in Taiwan
` Chia-En Lien; PLOS Neglected Tropical Diseases | https://doi.org/10.1371/journal.pntd.0010198 February 28, 2022
57,301 adult dengue cases reported in Taiwan between 2008–2015 were analyzed.
We assessed both outpatient and inpatient claims data of dengue patients from a week before
to a week after their dengue infections were confirmed under
Results
24.6% of dengue patients were prescribed an antibiotic during the 14 day-assessment period.
Antibiotics were prescribed in 6.1% and 30.1% of outpatient visits and inpatient admissions.
Antibiotic prescriptions were reduced by ~50% in epidemic years.
Among inpatients, advanced age, females, and major comorbidities were risk factors for
receipt of an antibiotic; antibiotics were used in 26.0% of inpatients after dengue was diagnosed.
Significant differences in antibiotic prescribing practices were observed among physicians
in outpatient settings but not in inpatient settings.
Risk factors for concurrent bacteremia in adult patients with dengue
Thein TL ; Journal of Microbiology, Immunology and Infection 2015
9,553 patients with dengue, 29 (0.3%) had bacteremia.
62.1% had concurrent bacteremia ( < 72 hr after admission).
The predominant bacteria were Staphylococcus aureus, one of which was a
methicillin-resistant strain.
Dengue shock syndrome occurred more frequently and hospital stay was
longer among cases than among controls.
80 patients, with an in-hospital mortality rate of 32.5%
categorized into Group I (BSI onset within 48 h after admission) 32 patients
Group II (between 48 h and one week) 32 patients
Group III (more than one week) 16 patients
Results
Group I were older (mean age: 75.6 yrs) and had a higher Charlson comorbidity index.
Group I : Major pathogens- Streptococcus spp. (28.9%, 11/38) and Escherichia coli (23.7%) Group II Major
pathogen- Enterobacteriaceae (38.2%, 13/34).
Fatal patients more often received inappropriate empirical antibiotic than the survivors (61.5% vs. 35.2%; p< 0.03).
MDR pathogens: Group 1 35.0 % Group II 25.0% Group III 75.0% p = 0.001
Inappropriate empirical antibiotic: Group 1 43.8 % Group II 43.8% Group III 68.8%% p= 0.05
Incidence, Characteristics and Risk Factors of Acute Kidney Injury among
Dengue Patients:A Retrospective Analysis Mallhi TH: PLOS ONE 2015
Independent risk factors for Acute Kidney Injury by multivariate analysis.
Acute Kidney Injury: Incident 7.2-13.3 %
Microscopic hematuria, proteinuria
Metabolic acidosis
Ending the neglect to attain the Sustainable Development Goals: a road map for neglected tropical diseases 2021−2030
https://www.who.int/publications/i/item/9789240010352 (Access 6 Jan 2022)
B. Guy et al. / Vaccine 29 (2011) 7229– 7241
Thank you for your attention

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03_Challenge in diagnosis and management of dengue in adults_Dr. Terapong_11 Jun 2022.pdffinal-copy_VV-MEDMAT-69501.pdf

  • 1. Challenges in Diagnosis and Management of Dengue in Adults: Interesting Dengue Cases ศ.นพ. ธีระพงษ์ ตัณฑวิเชียร MD., FRCP(Edin) อาจารย์หน่วยโรคติดเชื้อ ภาควิชาอายุรศาสตร ์ คณะแพทยศาสตร ์ จุฬาลงกรณ์มหาวิทยาลัย หัวหน้า Tropical Medicine Cluster, Health Supercluster, จุฬาลงกรณ์มหาวิทยาลัย ผู้ช่วยผู้อานวยการและรักษาการหัวหน้าฝ่ายวิจัยและบริการคลินิค สถานเสาวภา สภากาชาดไทย VV-MEDMAT-69501: Jun 2022
  • 2. 2 Disclosure ( 2016-2022) Prof. Terapong Tantawichien: has received support for Travel for International Conference (Bionet, Siam Pharm) Lectureships (GlaxoSmithKline, Pfizer, MSD, Roche Thai Meiji, Siam Pharm, Sanofi , Biovalys, Biogenetec……). Advisory board for zoster vaccine/pneumococcal vaccine (MSD), rabies vaccine (GSK), dengue vaccines (Sanofi, MSD, Takeda), influenza vaccine(Sanofi) Prof. Terapong Tantawichien: has received research funds from Sanofi (C. difficile vaccine) 2016-17 Medico (Plant-derived influenza vaccine) 2017-18 MPH, Thailand (shorten rabies PET) 2019-20 NSTDA/Bionet (Asia)-Spearhead project (Tdap: recombinant pertussis toxin)-2019-2023) Sanofi (Rabies vaccine:VRV-12) 2020-2021 Sanofi (Rabies vaccine: VRV-14) 2020-2021 Baiya ( Covid-19 vaccine) 2021-2023 Sanofi ( Yellow fever vaccine) 2021-2025 Jansen ( RSV vaccine) 2022-2024
  • 3. Overview • Dengue in Adults: Shifting of age groups in Thailand • Burden of Dengue in Adults: Focus on elderly and patients with co-morbidities • Diagnosis and Clinical Management in Adult Dengue: How to get better care
  • 4. • Significant co-circulation of the dengue viruses and • COVID-19 could have on health system in dengue endemic area • COVID-19 or dengue infection: Increase risk of infection and morbidity Differential diagnosis of dengue and COVID-19 False positive serological tests for dengue /COVID-19 infections Coinfections by COVID-19 and dengue virus: Increased severity • Impact of lockdown and social distancing on dengue epidemics Decreased/increased incidence of dengue
  • 5. Wartel TA; Asia Pacific Journal of Public Health 2017, Vol. 29(1) 7–16 Period(1980-2010) Incidence increased in all countries: Annual average % change (AAPC) 1980-2010: 6.7% in Thailand 10.4% in Vietnam 12.0% in Indonesia 18.1% in Malaysia 24.4% in Philippines Mortality: Increased in Indonesia (6.8%), Malaysia(7%), Philippines(29.2%) Decreased in Thailand(-1.3%), Vietnam (−2.5%) Indonesia Malaysia Philippines Thailand Vietnam 0.0 10.0 20.0 30.0 40.0 50.0 60.0 70.0 80.0 90.0 Age <15 Age >15 Proportion of Dengue Cases in Children and Adults, Thailand, 2000 - 2019
  • 6. National Notifiable Disease Information System, Brazil MoH, prepared by João Bosco Siqueira Jr. | 6 SPGLB.DENG.14.12.0103 ALL AGE GROUPS ARE AT RISK OF DENGUE DISEASE Thailand Dengue in Bangkok 2015 0 20 40 60 80 100 < 15 years % Mortality rate < 0.1% > 15 yrs
  • 7. Age-specific dengue seroprevalence in Mueang Rayong district, Thailand, according to the A) 1980, and B) 2010 serosurveys. Rodríguez-Barraquer I; Am J Epidemiol 2014 1980 - 96% exposed by age 11 years, 2010 -only 82% exposed by age 18 years.
  • 9.
  • 10. | 10 Dengue seroprevalence in HCW in Thailand (PRNT50 ) Seropositive : PRNT50 ≥ 10, Seronegative : PRNT50 < 10 • 400 HCW age 21-60 years old, (13% men, 87% women) • High dengue seroprevalence in study population, • 95% (379/400) have PRNT50 ≥10 for at least one serotypes • 11% (45/400) has PRNT50 < 10 for all serotypes WP. Vandepitte, Southeast Asian J Trop Med Public Health, Vol 50 No. 5 September 2019 Serotype 1 Serotype 2 Serotype 3 Serotype 4 By Serotype and Age Group
  • 11. 1 1 Angkana T. Huanga; PNAS 2022 Vol. 119 No. 20 e2115790119 https://doi, The mean age of dengue hemorrhagic fever (DHF) cases increased considerably in Thailand from 8.1 to 24.3 y between 1981 and 2017 (mean annual increase of 0.45 y). Alternative proposed explanations for this trend, such as - changes in surveillance practices, - reduced mosquito–human contact, - shifts in population demographics, have different implications for global dengue epidemiology
  • 12. Source: BOE, MoPH, Annual Epidemiology Surveillance Report (2010 to 2014), Report 506(2015) 0-4 17 12% 8 13% 14 16% 11 8% 6 12% 13 9% 5-9 41 29% 17 27% 19 22% 27 20% 8 16% 17 11% 10-14 29 21% 12 19% 20 23% 29 21% 8 16% 20 14% 15-24 29 21% 7 11% 19 22% 36 26% 12 24% 37 25% 25-34 8 6% 8 13% 11 13% 23 17% 5 10% 25 17% 35-44 7 5% 4 6% - 0% 4 3% 6 12% 20 14% 45-54 5 4% 6 10% 3 3% 3 2% 2 4% 13 9% 55-64 1 1% - 0% 1 1% 3 2% 2 4% 2 1% 65+ 2 1% 1 2% - 0% - 0% - 0% 1 1% Total 139 63 87 136 49 148 Number and percentage of reported Deaths from dengue per age group 2010 2011 2012 2013 2014 2015 ALL ALL 11% 17% 5% 7% 20% 24% Age group ALL ALL ALL ALL Deaths from Dengue in Thailand Deaths from Dengue in Thailand 2018 ( 6 months) Age Symptom Dengue Per 100,000 Dengue Death % 0 – 4 1,481 42.3 2 0.14 5 – 14 8,146 101.4 8 0.1 15 - 34 8,994 48.3 13 0.14 35 - 59 3,208 12.3 10 0.31 > 60 710 6.5 5 0.70
  • 13. Overview • Dengue in Adults: Shifting of age groups in Thailand • Burden of Dengue in Adults: Focus on elderly and patients with co-morbidities • Diagnosis and Clinical Management in Adult Dengue: How to get better care
  • 14.
  • 15. 28 adult dengue deaths, median age was 59 yrs and co-morbidities 75%. Probable dengue was diagnosed in 32.1% by WHO 1997 criteria and 78.6% by WHO 2009. The earliest warning sign was persistent vomiting at a median of 1.5 days. Hematocrit change >20% concurrent with platelet count <20 × 10^9/L was associated with the shortest interval to death at a median of 3 days. Only 35.7% of death cases fulfilled DHF criteria by WHO 1997 versus severe dengue in 100.0% by WHO 2009 criteria. Deaths were due to shock and organ failure. Acute renal impairment occurred in 71.4%, impaired consciousness 57.1% and severe hepatitis 53.6%. Confirmed adult dengue deaths in Singapore: 5-year multi-center retrospective study. Leo et al. BMC Infectious Diseases 2011, 11:123
  • 16.
  • 17.
  • 18. Dengue cases hospitalized;58.1% (2007 epidemic) 28.9% (2013–2014 epidemic) Less than 2% of hospitalized patients were admitted to the ICU. The proportions of dengue cases hospitalized and patients admitted to the ICU were highest in elderly aged > 65 y
  • 19.
  • 20.
  • 21. Risk predictors of progression to severe disease during the febrile phase of dengue: a systematic review and meta-analysis Sorawat Sangkaew; Lancet Infect Dis 2021;21: 1014–26 Findings Of 122 articles comprising 25 potential predictors were included in the meta-analyses. Female patients had a higher risk of severe dengue than male patients in the main analysis (16·2% VS 10·5%[OR=1·13] but not in the subgroup analysis of studies with children. Pre-existing comorbidities associated with severe disease were DM 31·3% VS 16·0%; crude OR 4·38 Hypertension 35·0% VS 20·6% OR 2·19 Renal disease 45·8% VS 16·0 OR 4·67 Cardiovascular disease 23·1% VS 8·6% OR 2·79
  • 22.
  • 23. References: 1. Toh ML, et al. Comorbidities increase In-Hospital Mortality in Dengue Patients in Brazil. Poster presented at API congress , 17 May 2017
  • 24. The average age of dengue patients admitted to ICU was around 42 years old, and 58% the male sex. 50% of these patients had medical comorbidities like DM, HT, cardiac disorders, chronic kidney,liver disease. 30% of patients had hypotension needing vasopressor therapy, 26%with RF needing ventilation, and 17% with renal failure needing renal replacement therapy. The ICU mortality was 20%. (? Medical comorbidity, pre-treatment , bacterial infection….)
  • 25. Overview • Dengue in Adults: Shifting of age groups in Thailand • Burden of Dengue in Adults: Focus on elderly and patients with co-morbidities • Diagnosis and Clinical Management in Adult Dengue: How to get better care
  • 27.
  • 28.
  • 29. J Clin Virol 2007 Southeast Asian J Trop Med Public Health 2013
  • 31. During the COVID-19 pandemic, distinguishing dengue from cases of COVID-19 in endemic areas can be difficult. Tertiary hospital: Strategy of routine COVID-19 testing for febrile patients with viral prodromes was used. (designated ward-PPE) , 11,086 admissions were screened for COVID-19; 868 cases of COVID-19/ 380 cases of dengue. 8.5% of suspected COVID-19 cases were tested for dengue serology due to a compatible overlapping syndrome, and dengue was established as an alternative diagnosis in 2% (207/10,218) of suspected COVID-19 cases that tested negative. 8 COVID-19 cases with likely false-positive dengue serology and one probable coinfection. From April to May 2020, 251 admissions presenting as viral prodromes with no RTI 15 cases had COVID-19, and 2/15 had false-positive dengue IgM.
  • 32. Potential antigenic cross-reactivity between SARS-CoV-2and Dengue viruses Yaniv Lustig; Clin Infect Dis 2020 Serology characteristics of 14 patients with covid-19 (n 55) and false positive dengue serology SD Bioline PanBio
  • 33. Tun-Linn Thein; Am. J. Trop. Med. Hyg., 90(6), 2014, pp. 984–987 1,921 confirmed adult dengue patients between 2005 and 2008. We found that severe neutropenia, defined as ANC < 0.5 + 109/L, was found in 11.8% with a median duration of 1 day. ANC nadir occurred on illness day 5. Severe neutropenia was not predictive of more severe disease and not associated with secondary bacterial infections, prolonged hospital stay, prolonged fever, or fatal outcome.
  • 34.
  • 35. Anon Srikiatkhachorn ; Thromb Haemost 2009 Warning signs Dengue/severe dengue Warning signs Dengue/severe dengue Dengue fever Dengue hemorrhage fever
  • 38. DHF 14- yr boy DF 16- yr boy “Dengue is one disease entity with different clinical presentations and often with unpredictable clinical evolution and outcome” Who Guideline 2009
  • 40. RCPT guideline- Thailand Indications for hospitalization ( one of the followings ): • - Signs/symptoms that physicians considers make the admission of the patient necessary (eg. intractable nausea/vomiting, serious illness etc.) - Significant bleeding eg. gastrointestinal bleeding etc. - Dengue shock syndrome (DSS) - Hematocrit > 50 % - Platelet < 20,000/ mm3 ( < 20x109/L) - AST or ALT > 500 IU/mL - Acute renal failure, hepatic failure, heart failure, alteration of consciousness, severe hypoxemia - Pregnant woman - Morbid obesity - Patients could not follow up as out-patient setting
  • 41. Management of Adult Dengue Bleeding in adult dengue: Severe Gastrointestinal bleeding Anticoagulant Prophylaxis platelet transfusion Leakage syndrome (DHF) and DSS in adults Fluid overload/myocardial injury Liver injury and GI manifestations Hepatitis / Acetaminophen usage Acute hepatic failure Others: Renal failure- metabolic acidosis Co-infection-bacteremia
  • 42. If major bleeding occurs it is usually from GI tract, and/or vagina in adult females. Internal bleeding may not become apparent for many hours until the first black stool is passed. Patients at risk of major bleeding are those who had: – Prolonged/refractory shock; – Hypotensive shock and renal or liver failure and/or severe and persistent metabolic acidosis; – Received non-steroidal anti-inflammatory agents – Pre-existing peptic ulcer disease – Received anticoagulant therapy – Trauma, including intramuscular injection.
  • 43. Day of fever 4 5 6 7 8 9 39 BT 38 37 21 year-old patient (male) DEN - IgM positive stable N/V cough hematemesis/melena hematochexia diarrhea Rx PRC endoscope (DU active bleeding) myalgia platelet conc. vagotomy/pyloroplasty Hct WBC/mm3 N / L (%) Platelet/mm3 CXR 40 5500 74/15 150,000 40 4700 65 / 28 42,000 26 59,000 normal 21 19 25 30 32 12500 61 / 38 72,000(PT/PTT-N) 69,000 97,000 normal BP
  • 44. Characteristics and predictors for gastrointestinal hemorrhage among adult patients with dengue virus infection: Emphasizing the impact of existing comorbid disease(s) Wen-Chi Huang: PLOS ONE 2018; https://doi.org/10.1371/journal.pone.0192919 Retrospective study : 1300 adults dengue 175 (mean age, 56.5±13.7 yrs) patients with GI bleeding 1,125 (mean age, 49.2±15.6 yrs) without GI bleeding (controls) Results 175 patients with GI bleeding, DHF was found in 119 pts (68%). Endoscopic exam: Gastric ulcer 52%, erythematous gastritis 33%, duodenal ulcer 29%, erosive gastritis 29%, hemorrhagic gastritis 14.3% Overall, GI bleeding died, giving an in-hospital mortality rate of 5.1%. Multivariate analysis: Risk of GI bleeding: Age> 60 years (OR 1.663) End stage renal disease with comorbidities (OR: 9.405) Previous stroke with comorbidities (OR: 9.772) Gum bleeding (OR: 1.732), petechiae (OR: 2.109) Platelet count <50×109 cells/L (OR: 3.419)
  • 45. Chiu YC, Am J Trop Med 2005 Patients having PU with recent hemorrhage require more transfusions with PRBCs and FFP for management of UGI bleeding than do those without recent hemorrhage. PU with recent hemorrhage is encountered during an endoscopic procedure, endoscopic injection therapy is not an effective adjuvant treatment of hemostasis in dengue patients with UGI bleeding.
  • 46. A FATAL CASE OF SPONTANEOUS RUPTURE OF THE SPLEEN DUE TO DENGUE VIRUS INFECTION: CASE REPORT AND REVIEW. Southeast Asian J Trop Med Hyg 2008 Apatcha Pungjitprapai, Terapong Tantawichien.
  • 47. Severe bleeding can be recognized by: – Severe overt bleeding, regardless of Hct level – Decrease in Hct after fluid resuscitation together with unstable hemodynamic status; – Refractory shock that fails to respond to consecutive fluid resuscitation of 40-60 ml/kg – Hypotensive shock with low/normal Hct before fluid resuscitation – Persistent or worsening metabolic acidosis + a well-maintained systolic blood pressure, especially in those with severe abdominal tenderness and distension. Jacqueline Deen, Lucy Lum, Eric Martinez, Lian Huat Tan. Dengue: guidelines for diagnosis, treatment, prevention and control -- New edition. WHO 2009
  • 48. Risks of bleeding: INR > 3 Age > 65 years, uncontrolled hypertension bleeding tendencies, Abnormal renal or liver function, Previous stroke, Labile INR while onwarfarin, Concomitant use of NSAIDs Risks of valvular thrombosis: (ex. thromboembolism) INR < 2 Prosthetic mitral valve replacement, Use of mechanical valves, thrombophilia, atrial fibrillation, low left ventricular ejection fraction, Prior thromboembolism, Early post-operative period after valvular replacement Lionel Hon Wai Lum; International Journal of Cardiology 199 (2015) 432–434
  • 49. Lack of efficacy of prophylactic platelet transfusion for severe thrombocytopenia in adults with acute uncomplicated dengue infection. Lyn DC; Clin Infect Dis 2009 Thrombocytopenia in dengue infection raises concerns about bleeding risk. Of 256 patients with dengue infection who developed thrombocytopenia (platelet count, < 20 x 103 platelets/microL) without prior bleeding, 188 were given platelet transfusion. Subsequent bleeding, platelet increment, and platelet recovery were similar between patients given transfusion and patients not given transfusion. Prophylactic platelet transfusion was ineffective in preventing bleeding in adult patients with dengue infection.
  • 50. Open-label, randomized, superiority trial: We recruited patients aged > 21 years who had laboratory-confirmed or probable dengue and thrombocytopenia (≤20 000 platelets per μL), without persistent bleeding. Results: Clinical bleeding by day 7/ hospital discharge 21% in transfusion group VS 26% in control group (risk difference –4・98% ; RR 0.8 [95% CI 0.56-1.17]; p=0.16). 13 adverse events in transfusion group VS 2 in the control group (5.81% ; RR 6.26; p=0・0064).
  • 51. Cardiovascular manifestations - Plasma leakage in DHF/DSS-Hypotension Volume overload/ pulmonary edema Co-morbidity- CHF, coronary heart disease - Cardiac complications- are not uncommon but it was self-limiting, acute myocarditis may be clinically severe. - Myocardial dysfunction/myocarditis Decreased EF, diastolic volume, ST-T change, increased cardiac enzyme -Cardiac arrhythmia-Tachy/Bradyarrhythmia Sinus bradycardia, SVT, atrial fibrillation APC, PVC, 1st degree AV block, 2nd degree AV block Mobitz type 1 Apichai K; Intensive Care Med 2003 V. LA-ORKHUN; Annals of Tropical Paediatrics (2011) 31, 123–128 Cardiovascular sequelae of dengue fever: a systematic review Abdur Rahim; Expert Rev Cardiovasc Ther . 2022 Jun 2;1-15. ECG abnormalities (30.6%): Sinus bradycardia (8.8%), Nonspecific ST-T changes (8.6%), ST depression (7.9%), T-wave inversion (2.3%). Mechanical sequelae were present in 10.4%, including left ventricular (LV) systolic dysfunction (5.7%), and myocarditis (2.9%).
  • 52. Management of adult Dengue : Royal Colladge Physician of Thailand Guideline 2013 Plasma leakage( any one of this ) 1.Hct≥50 % 2.Evidence of plasma leakage ➢hemoconcentration ( Hct ≥20% compare to previous Hct) ➢Pleural effusion ➢Hypotension ➢Serum albumin Plasma leakage+ Dengue : clinical stage 2 ➢Fluid: crytaloid: NSS, RLS etc ➢Close monitoring ➢Look for : hypotension, pulse pressure ≤20 mmHg, poor tissue perfusion BP normal + pulse pressure > 20 mmHg Rx Oral/IV fluid :adjust rate by ➢Clinical observation ➢Follow the Hct ➢ Urine volume and urine specific gravity
  • 53. Causes of fluid overload – Excessive and/or too rapid IV fluids; – Incorrect use of hypotonic – Inappropriate use of large volumes of IV fluids in patients without leakage/ severe bleeding – Continuation of IV fluids after plasma leakage has resolved (24–48 hours from defervescence) – co-morbid conditions such as congenital or ischaemic heart disease, chronic lung and renal diseases. WHO Guideline 2009
  • 54. Mirinda CH; Clin Infect Dis 2013 81 dengue pts (mean age 32yr) –12 patients (15%): elevated biomarker levels. Compared to controls, Higher leukocyte (P < .001) and platelet counts (P = .005); higher CRP(P = .02), and a lower VL (P = .03). There was no difference according to clinical dengue classification; DF/DHF/DSS ; duration of symptoms; or prevalence of secondary infection between the 2 groups. 2 patients died secondary to cardiogenic shock before imaging studies. Necroscopic findings were compatible to myocarditis in both , 10 patients who underwent echocardiography: Depressed left ventricular ejection fraction (LVEF) was identified in 1, left ventricular segmental abnormalities with preserved LVEF in 2, and an important pericardial effusion with tamponade in another.
  • 55.
  • 56. 56 Major acute cardiovascular events after dengue infection–A population-based observational study Kai-Che Wei; PLOS Neglected Tropical Diseases | https://doi.org/10.1371/journal.pntd.0010134 February 7, 2022 The Incident rate ratio (IRR) of MACEs was 17.9 (95% CI 15.80–20.37) during the first week after the onset of DENV infection observed from 1,244 eligible patients. IRR were significantly higher for hemorrhagic stroke (10.9, 95% CI 6.80–17.49), ischemic stroke (15.56, 95% CI 12.44–19.47), AMI (13.53, 95%CI 10.13–18.06), and heart failure (27.24, 95% CI 22.67–32.73). No increased IRR was observed after day 14.
  • 57. | 57 Footer goes here A 24-year-old male presented fever and N/V for 4 days. PH : Healthy, no alcohol drinking PE : Conscious, not pale , no jaundice VT BT 38.9°c PR 80/min BP –stable RR 24/min Others – WNL Lab : Hct 42 % WBC 4200/cumm N 65% L 30%M 5 % Platelet 80,000 / cumm BUN/Cr 10/0.8 SGOT / SGPT 5650/2690 Electrolyte -WNL
  • 58. - Nausea/ vomiting - Diarrhea - GI bleeding - Liver complication: Abnormal transaminase ( increased AST and ALT) Viral factor (DEN3,DEN4) Prolonged shock , ischemic hepatitis Reye’s syndrome Drug-induced liver injury Co-infection: Viral hepatitis A, B,C,E Pre-existing liver diseases - Ascites, acute appendicitis GI Manifestations in dengue
  • 59. Liver function test in DF/DHF patients Kuo CH* Kalaganaroaj S** Tantawichien T. DF DF DHF DF DHF n=230 n=20 n=21 n=38 n=30 Age:Mean+SD AST : Mean+SD Range ALT : Mean+SD Range Bilirubin : Abnormal/range Akaline phasphatase Abnormal/range 41+12 220+341 17-3210 146+178 8-1177 7.2%0.2-35 16%320-536 3.7+1 64+46 35+18 4.3+1.2 124+166 51+59 28.6+13.2 258+436 17-2128 184+255 19-1171 0% all<1.5 23.4+7.6 399+554 15-2580 261+321 3-1382 1 case (5) all<1.5 *Kuo CH; Am J Trop Med Hyg 1992 **Kalayanarooj S; JID 1997
  • 60. Patterns and causes of liver involvement in acute dengue infection Fernando et al. BMC Infectious Diseases (2016) 16:319 AST ALT AST/ALT ratio
  • 61. Effect of Standard Dosage of Paracetamol versus Placebo as An Antipyretic Therapy on Transaminitis in Adult Dengue Infection: A Randomized Controlled Trial Vasikasin V: Presented in RCPT 2018 Multicenter randomized ,double trial, placebo control: 125 hospitalized adult patient (mean age 27 + 10 yrs) with laboratory-confirmed dengue If body temp. > 38 °c – received paracetamol 500 mg or placebo 500 mg every 4 hrs Primary outcome- AST and ALT more than 3 times Results Median daily dosage of paracetamol 1.5g ( IQR= 0.8-2g) - Significant higher rate of transiminitis (increased AST,ALT) in paracetamol group compared with placebo (22% vs 10%; incidence rate ratio 3·77,p= 0·011). - The change of AST/ALT in the paracetamol group > placebo group (mean difference AST= 12·43 U/L per day, p<0·0001 ALT=; 7·40 U/L per day, p=0·0001 No significant change of body temp. and pain score
  • 62. Day of fever 4 5 6 7 8 9 10 11 39 BT 38 37 BP stable Bradycardia Fever no diarrhea Anti HAVIg M N/V N/V N/V Anti HB c IgM AntiHCV Anti HIV Others Hct 42 44 WBC/mm 4200 2,200 N/L (%) 65 /25 100 / 70 Platelet/mm3 80.000 47,000 SGOT/SGPT 5650/2690 849/862(TB/DB 4.5/3.5) 324/287( TB 2) AP 152 Albumin 3.5 Hemoculture neg no pleural effusion 24 year - old patient (male) 80/
  • 63. Acute hepatic failure in Hemoglobin H dis and DHF Recent suggestions for the treatment of dengue patients with acute liver failure N-acetylcysteine (NAC) Providing temporary liver support – Artificial liver support Treeprasertsuk S; Southeast Asian J Trop Med Public Health 2015 World J Hepatol 2021 December 27; 13(12): 1968-1976
  • 64. A Thai male 34-year-old patient underlying Ch Hepatitis B And alcoholic drinking – no treatment Ultrasound- mild splenomegaly, SGOT/SGPT-WNL CC: Fever 4 days PTA PI: 4 days PTA high fever, diarrhea, N/V and myalgia 2 days PTA fever, jaundice, yellow stool ( he ate paracetamol 20 tab and cpm+pseudoephrindine 8 tab ) PE: Good consciousness, not pale, mark jaundice VT- PR 98/min, RR 24/min, BP 150/80mmHg, BT 38 °c Chest/heart- WNL Abdomen- soft, not tender, liver 2 FB below RCM(span 15 cm) no ascites, BS normal LAB: Hct 44.4 % WBC 9,000/mm3 N 59,L23 , Atypical L 6 Platelet 90,000 /mm3 Hct 43 % WBC 13,000/mm3 N 59, L30 ,Platelet 49,000 /mm3 Na 131, K4.3, Cl 92, HCO3 27 LFT- TB 8.2mg%, DB 6.7mg%,SGOT/SGPT 2333 / 1404 , Alb 3.7 mg% ,BUN/Cr 24/1 mg%, PT 17.3/11.2 CPK 118
  • 65. Dengue IgM/IgG- rapid test Positive Dengue NS1 –positive Dengue IgM-positive Dengue IgG-positive HbsAg -positive AntiHBc-positive AntiHCV-negative US- Cirrhosis, no ascites
  • 66.
  • 67. Treatment Supportive treatment, hydration Drugs : Acetaminophen,Anti-gastritis ; H2 blocker,NSAIDs Unnecessary drugs; muscle relaxant…… Antibiotic treatment ( 20-30 % case ) Transfusion : Platelet transfusion, PRC, FFP Procedure : catheter, NG tube, endoscopy, operation Adjunctive therapy : Steroid, IVIG Carbazochrom sodium sulfonate (AC-17), Recombinant activated factor VII, Desmopressin
  • 68. 6 8 Population-based assessment of factors influencing antibiotic prescribing for adults with dengue infection in Taiwan ` Chia-En Lien; PLOS Neglected Tropical Diseases | https://doi.org/10.1371/journal.pntd.0010198 February 28, 2022 57,301 adult dengue cases reported in Taiwan between 2008–2015 were analyzed. We assessed both outpatient and inpatient claims data of dengue patients from a week before to a week after their dengue infections were confirmed under Results 24.6% of dengue patients were prescribed an antibiotic during the 14 day-assessment period. Antibiotics were prescribed in 6.1% and 30.1% of outpatient visits and inpatient admissions. Antibiotic prescriptions were reduced by ~50% in epidemic years. Among inpatients, advanced age, females, and major comorbidities were risk factors for receipt of an antibiotic; antibiotics were used in 26.0% of inpatients after dengue was diagnosed. Significant differences in antibiotic prescribing practices were observed among physicians in outpatient settings but not in inpatient settings.
  • 69. Risk factors for concurrent bacteremia in adult patients with dengue Thein TL ; Journal of Microbiology, Immunology and Infection 2015 9,553 patients with dengue, 29 (0.3%) had bacteremia. 62.1% had concurrent bacteremia ( < 72 hr after admission). The predominant bacteria were Staphylococcus aureus, one of which was a methicillin-resistant strain. Dengue shock syndrome occurred more frequently and hospital stay was longer among cases than among controls.
  • 70. 80 patients, with an in-hospital mortality rate of 32.5% categorized into Group I (BSI onset within 48 h after admission) 32 patients Group II (between 48 h and one week) 32 patients Group III (more than one week) 16 patients Results Group I were older (mean age: 75.6 yrs) and had a higher Charlson comorbidity index. Group I : Major pathogens- Streptococcus spp. (28.9%, 11/38) and Escherichia coli (23.7%) Group II Major pathogen- Enterobacteriaceae (38.2%, 13/34). Fatal patients more often received inappropriate empirical antibiotic than the survivors (61.5% vs. 35.2%; p< 0.03). MDR pathogens: Group 1 35.0 % Group II 25.0% Group III 75.0% p = 0.001 Inappropriate empirical antibiotic: Group 1 43.8 % Group II 43.8% Group III 68.8%% p= 0.05
  • 71. Incidence, Characteristics and Risk Factors of Acute Kidney Injury among Dengue Patients:A Retrospective Analysis Mallhi TH: PLOS ONE 2015 Independent risk factors for Acute Kidney Injury by multivariate analysis. Acute Kidney Injury: Incident 7.2-13.3 % Microscopic hematuria, proteinuria Metabolic acidosis
  • 72. Ending the neglect to attain the Sustainable Development Goals: a road map for neglected tropical diseases 2021−2030 https://www.who.int/publications/i/item/9789240010352 (Access 6 Jan 2022)
  • 73.
  • 74. B. Guy et al. / Vaccine 29 (2011) 7229– 7241
  • 75. Thank you for your attention